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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease VI.
Ludvik, Matěj ; Chlebek, Jakub (advisor) ; Šafratová, Marcela (referee)
Ludvik M., Papaver rhoeas L. (Papaveraceae) alkaloids and their activity related to Alzheimer disease VI., diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové 2023, number of pages 69. This diploma thesis was focused on alkaloids from combined fractions 13-15 of diethylether extract from Papaver rhoeas L. The methods used for extraction of the alcaloids include flash chromatography and preparative thin-layer chromatography. The structures of isolated compounds were determined by using mass spectrometric and spectrophotometric methods (GC-MS, NMR and optical rotation). Alkaloids were identified as galanthamine and N,N-dimethyltryptamine. Subsequently, N,N-dimethyltryptamine was tested for its biological activity against human cholinesterases, specifically acetylcholinesterase and butyrylcholinesterase. Galanthamine was not tested on ability to inhibit cholinesterase, since the compound has been already tested on this activity at the Department of Pharmacognosy and Pharmaceutical Botany. N,N-dimethyltryptamine showed mild inhibitory activity against butyrylcholinesterase (IC50 = 44,14 ± 1,76) and no activity against acetylcholinesterase (IC50 = >100). Despite its mild activity towards butyrylcholinesterase, N,N-dimethyltryptamine can't be used in therapy of Alzheimer's disease,...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease V.
Dušánková, Zita ; Chlebek, Jakub (advisor) ; Hošťálková, Anna (referee)
Dušánková Z.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs diesease V.; Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognozy and Pharmaceutical Botany, Hradec Králové 2023, pages 72. The aim of this diploma thesis was focused on isolation of alkaloids from a combined fraction 7-8 of an alkaloidal diethyl ether (Et2O) extract of aerial parts of Papaver rhoeas L. (Papaveraceae). Column chromatography (flash chromatography), planar chromatography (preparative TLC) and crystallization were used for the isolation of alkaloids. The structures of isolated substances were elucidated using NMR, GC-MS methods and optical rotation. Isolated alkaloids were identified as ZD-1, (+)-3,4-dehydrotheaspirone, (±)-juziphine, (+)-lirinidine and protopine. Alkaloids were tested for biological activity against enzymes (acetylcholinesterase, butyrylcolinesterase and prolyl oligopeptidase). (+)-3,4-Dehydrotheaspirone, (±)-juziphine, and protopine did not show significant inhibitory activities against cholinesterases (IC50 values >100 µM). Protopine was also inactive against prolyl oligopeptidase (IC50 >1000 µM ). (+)-Lirinidine showed a moderate inhibitory activity against BuChE (IC50 value of 23,45 ± 0,55 µM), towards...
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Vinca minor L. alkaloids and their biological activity III.
Valová, Dominika ; Chlebek, Jakub (advisor) ; Hradiská Breiterová, Kateřina (referee)
Valová D.: Vinca minor L. alkaloids and their biological activity III. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové, 2020, 75 p. Alzheimer's disease (AD) is a progressive, neurodegenerative disorder and it's the most common form of dementia. Because we're still not able to treat the cause of disease, searching for a new substance is relevant. This thesis is focused on isolation of alkaloids from a Vinca minor L. alkaloidal extract as a potential drug. The preparation and column chromatography of the summary extract were performed by Ing. Miroslav Ločárek as a part of his doctoral studies. Subsequent preparative TLC led to the isolation of three compounds. The chemical structures of the isolated alkaloids were elucidated by means of optical rotation, NMR and MS analyses and by comparison of the obtained data with those in the literature. One of the compounds was determined as(-)-vincine, other two compounds have not been isolated yet. Isolated compounds were also tested for their biological activity. Vincine, DV-1 a DV-3 were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Additionally, vincine and DV-3 were also tested for their inhibitory activity on prolyl...
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Centaurea cyanus L. (Asteraceae) alkaloids and their biological activity related to Alzheimer's disease
Drabbová, Adriana ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Drabbová, A.: Title of Diploma Thesis: Centaurea cyanus L. (Asteraceae) alkaloids and their biological activity related to Alzheimer's disease. Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové 2020. Ethyl acetate and chloroform alkaloids extracts were prepared from Centaurea cyanus L. seeds. A novel alkaloid AD-1 (Adrabbin) was isolated from the ethyl acetate extract by common chromatografic methods (column chromatography, preparative TLC). Its structure was elucidated by mass spektrometry, NMR analysis and determination of optical rotation. The alkaloid AD-1 (Adrabbin) possesses a unique structure which consists of a cyclic indole moiety. Also LC-MS analysis of fractions obtained by flash chromatography was performed. In those fractions were detected molecular ions related to compounds previously isolated from other Centaurea species. Alkaloid AD-1 (Adrabbin) was tested on ability to inhibit human cholinesterases, prolyl oligopeptidase and gylcogen synthase kinase 3β. The compound was considered against human cholinesterases inactive (IC50 values > 100 µM). Interestibgly, the alkaloid inhibited prolyl oligopeptidase the same intensity as a standard berberine (AD-1: IC50 143,0 ± 6,0 µM; berberin: IC50 142,0 ± 21,0 µM). The novel compound...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease IV.
Gergely, Eszter ; Chlebek, Jakub (advisor) ; Hradiská Breiterová, Kateřina (referee)
Gergely, E.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease IV. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy and Pharmaceutical Botany, Hradec Králové 2022, 61 pages. A chloroform alkaloid extract of aerial parts of Papaver rhoeas L. (Papaveraceae) showed a significant inhibitory activity on human butyrylcholinesterase (IC50hBuChE = 3,94 ± 0,35 µg/ml) [1,2]. hBuChE represents a key enzyme playing an important role in the pathogenesis of Alzheimer's disease. The main aim of this study was to isolate pure alkaloids by bio-guided assay using flash chromatography and preparative TLC, elucidate their structures (MS, NMR, and optical rotation) and cholinesterase inhibitory activity with Ellman's spectrophotometric method. Prediction of possibility of the molecules' crossing through blood-brain barrier (BBB) via logBB was calculated. Potential non-cytotoxicity of the most active compound was screened on selected nine cancer cell lines and one non-cancer cell line MRC-5. The identified isolated alkaloid (+)-caaverine showed a promising and selective hBuChE inibition (IC50hBuChE = 4,09 ± 0,50 µM and IC50hAChE > 100 µM, respectively) and should be able to cross the BBB (logBB = 0,372) by...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease III.
Bučková, Anna ; Chlebek, Jakub (advisor) ; Suchánková, Daniela (referee)
Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease III. ABSTRACT Bučková, A.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease III.; Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy and Pharmaceutical Botany, Hradec Králové 2022, 59 pages The aim of this diploma thesis was to fractionate the combined extract (CHCl3 +EtOAc + I- ) from Papaver rhoeas L. using flash chromatography and subsequently, to isolate alkaloids from the chosen factions by preparative TLC. The chemical structures of the isolated compounds were determined by spetrometric and spectroscopic methods (MS, NMR and optical rotation). Alkaloids were identified as (+)-rhoeadin, (+)-rhoeagenin a (+)-isorhoeagenin. After structure elucidation, the alkaloids were tested in vitro for inhibitory activity towards enzymes that are playing part in the pathogenesis of the Alzheimer's disease (acetylcholinesterase, butyrylcholinesterase a prolyloligopeptidase). Based on the results, the studied alkaloids seem to be inactive towards chosen enzymes (values IC50 > 100 µM). Key words: Papaver rhoeas, Papaveraceae, Alzheimerʼs disease, acetylcholinesterase, butyrylcholinesterase, prolyl...
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Alkaloids of Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity III.
Rýdlová, Kateřina ; Chlebek, Jakub (advisor) ; Cahlíková, Lucie (referee)
Rýdlová Kateřina: Alkaloids Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity III. Diploma thesis 2017. Charles university in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The aim of this work was isolation of compounds from the selected fraction ND 3 - 5 obtained by column chromatography of a Narcissus 'Dutch Master' alkaloid extract. Preparation of the extract and its column chromatography was performed by Mgr. Daniela Hulcová as a part of her doctoral study. Two substances NDM-1 and NDM-2 were isolated from fraction ND 3 - 5 by column chromatography and preparative TLC. The structures were determined as (+)-masonine and (+)-homolycorine on the basis of NMR, GC-MS analysis, optical rotation and their comparison with literature data. Isolated alkaloids were tested on inhibitory activity against human erythrocyte acetylcholinesterase, plasma butyrylcholinesterase and prolyloligopeptidase. Activity of alkaloids was expressed as IC50 values: (+)-masonine (IC50 AChE = 305 ± 34 μM, IC50 BuChE = 229 ± 24 μM, IC50 POP = 314 ± 34 μM), (+)-homolycorine (IC50 AChE = 63.7 ± 4.3 μM, IC50 BuChE = 151 ± 20 μM, IC50 POP = 173 ± 41 μM). In comparison with standards of galanthamine (IC50 AChE = 1.710 ± 0.1 μM, IC50 BuChE = 42.3 ± 1.3 μM),...
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Alkaloids from Narcissus pseudonarcissus L. cv. Dutch Master and their cholinesterase and prolyl oligopeptidase inhibitory activity.
Farkašovský, Marek ; Chlebek, Jakub (advisor) ; Siatka, Tomáš (referee)
Farkašovský Marek: Alkaloids from Narcissus pseudonarcissus L. cv. Dutch Master and their cholinesterase and prolyl oligopeptidase inhibition activity. Rigorous thesis 2017, Charles university, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The content of this work was isolation of minimum two compound from alkaloid fraction ND 3 - 5/2, obtained by column chromatography of Narcissus pseudonarcissus L. cv. Dutch Master alkaloid extract. Preparation of extract and its column chromatography was performed by Mgr. Daniela Hulcová as a part of her doctoral studies. Two different alkaloids were isolated with preparative TLC method. Their structure was determined with optical rotation, MS (EI, ESI), 1H NMR and 13C NMR analysis. Obtained data were compared with facts with those in literature. The first isolated compound was lycorine type alkaloid O-acetylpluvine. Its inhibition activity compared to positive standards (galanthamine, huperzine A, physostigmine, berberine and Z-pro-prolinal) was mild - IC50 AChE: 684 ± 54 µM, IC50 BuChE: 603 ± 49 µM, IC50 POP ˃1000 µM. From the point of its cholinesterase and POP inhibition, this results make O-acetylpluvine unusable compound in treatment of AD. The second isolated compound was a new alkaloid, which has not been...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease I.
Bulvová, Leontina ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Bulvová, L.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease I. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2017. The aim of this study was to process the summary alkaloidal extract of aerial parts of Papaver rhoeas L.; to isolate contained alkaloids using chromatographical methods; to identify them and to determine their inhibitory activity towards human enzymes acetylcholinesterase, butyrylcholinesterase and prolyloligopeptidase. Two alkaloids (+)-rhoeagenine and LB-2 were isolated, and the structure of LB-2 (its absolute configuration) is being determined nowadays. In vitro biological assays of these alkaloids found the following results: (+)-rhoeagenine (IC50 AChE ˃ 1000 μM, IC50 BuChE = 230 ± 10 μM, IC50 POP = 878 ± 45 μM) and LB-2 (IC50 AChE ˃ 1000 μM, IC50 BuChE = 314 ± 13 μM, IC50 POP = 706 ± 2 μM). The determined IC50 values of isolated alkaloids were compared with inhibitory standards of cholinesterases galanthamine (IC50 AChE = 1,71 ± 0,065 μM, IC50 BuChE = 42,30 ± 1,30 μM), huperzine A (IC50 AChE = 0,033 ± 0,001 μM, IC50 BuChE > 1000 μM, IC50 POP > 1000 μM) and rivastigmine (IC50 AChE = 0,037 ± 0,001 μM, IC50 BuChE = 0,0033 ± 0,0003...
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Alkaloids of Narcissus'Dutch Master ' (Amaryllidaceae) and their biological activity. II.
Dvořáková, Zdeňka ; Chlebek, Jakub (advisor) ; Ločárek, Miroslav (referee)
Dvořáková Zdeňka: Alkaloids of Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity II. Diploma thesis 2016, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The content of this work was isolation of compounds from the selected fraction ND-6 obtained by column chromatography of Narcissus 'Dutch Master' alkaloid extract. Preparation of extract and its column chromatography was performed by Mrg. Daniela Hulcová as part of her doctoral studies. By the means preparative TLC was from fraction ND- 6 homolycorine type alkaloid (+)-O-methyllycorenine gained. Its structure was determined on the basis NMR, GC-MS analysis and optical rotation. The obtained data were compared with facts in known literature. By the isolated alkaloid was determined its cholinesterase inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Its inhibitory activity was expressed as IC50 (M) and compared with known standards galanthamine, physostigmine, and Huperzine A. This alkaloid is inactive against cholinesterase (IC50 AChE > 1000 M, IC50 BChE > 1000 M). On the basis of gained results, we can evaluate this alkaloid from the point of view of cholinesterase inhibition as potentially unusable in the treatment of AD. Key...
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